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T M Brown

Publications and source records attributed to T M Brown.

At least 55 records · Page 3Linked to original sources
PubMed1996

Pathophysiology and management of the serotonin syndrome.

OBJECTIVE: To review the symptoms, pathophysiology, and treatment of the serotonin syndrome (SS). DATA SOURCES: A MEDLINE search (1957-1995) of the English-language literature pertaining to the SS was performed. Additional literature was obtained from reference lists of pertinent articles identified through the search. STUDY SELECTION AND DATA EXTRACTION: All articles were considered for possible inclusion in the review. Pertinent information, as judged by the authors, was selected for discussion. DATA SYNTHESIS: The SS, an occasionally fatal disorder, is characterized by symptoms such as mental status changes, seizures, myoclonus, and blood dyscrasias. Both the central and peripheral serotonergic systems and several serotonin receptor types are involved in the symptomatology of the SS. The pathogenesis of SS may be due to endogenous as well as iatrogenic deficits in peripheral serotonin metabolism, a stimulus for release of serotonin, and interactions with other neurotransmitter systems. Lorazepam, serotonin-blockers, and nitroglycerin have been used successfully to treat SS. CONCLUSIONS: The SS is increasingly recognized and reported in the literature. Clinical and basic science research have increased our understanding of the pathophysiology, conditions, and agents that may predispose to the development of the syndrome. Newer treatment strategies are discussed.

Animals↗
PubMed1996

SSRI withdrawal.

Explore the source record for details and available documents.

Humans↗
PubMed1995

Discontinuities in the evolution of Pseudomonas putida cat genes.

The organization and transcriptional control of chromosomal cat genes (required for dissimilation of catechol by the beta-ketoadipate pathway) in the Pseudomonas putida biotype strain (ATCC 12633) are reported. Nucleotide sequence reveals that catR is separated by 135 bp from the divergently transcribed catBC,A; catC begins 21 nucleotides downstream from catB, and catA begins 41 nucleotides downstream from catC. This contrasts with the gene arrangement in other bacteria, in which catA lies several kilobases upstream from catB. Properties of Tn5 mutants confirmed earlier suggestions that catR is a transcriptional activator and indicated that catA is activated by CatR independently of its activation of catBC. CatR binds to both a DNA fragment containing the catR-catB intergenic region and another DNA fragment containing catC. Pseudomonas strain RB1 resembles P. putida in some respects. Divergence of the two Pseudomonas chromosomes was revealed as nucleotide substitution of about 10% after alignment of known portions of catR,BC,A. Divergent transcriptional controls are suggested by a cluster of nucleotide sequence modifications in Pseudomonas strain RB1 which disrupt a stem-loop structure directly upstream of catB in the P. putida chromosome. Abrupt divergence of the catR,BC,A nucleotide sequences was achieved during evolution by insertion of an 85-bp palindromic genetic element uniquely positioned downstream from P. putida catR and counterpoised by insertion of a similar palindromic sequence in the Pseudomonas strain RB1 catB-catC intergenic region. Properties of the palindromic genetic element suggest that it may serve functions analogous to those of repetitive extragenic palindromic sequences and enteric repetitive intergenic consensus sequences in enteric bacteria.

Amino Acid Sequence↗
PubMed1995

Proteinuria in patients with sleep apnea.

BACKGROUND: Proteinuria severe enough to be in the nephrotic range has been noted on occasion in patients with obstructive sleep apnea (OSA), but it is not known what factors are related to the severity of proteinuria in these patients. This study was conducted to determine if the severity of proteinuria is related to the number of apneas. METHODS: The level of proteinuria was determined by the dipstick method in 407 patients in whom OSA had been diagnosed. The apnea-hypopnea index (AHI) was calculated in each patient after all-night polysomnography. Sleep apnea was defined as the presence of at least 30 apneas during a 6- to 8-hour monitoring period and an AHI greater than 15. RESULTS: The apnea-hypopnea index in patients without proteinuria was similar to that of patients with 1+ to 3+ proteinuria. However, the AHI was significantly greater in the 9 patients with 4+ proteinuria. CONCLUSIONS: While severe proteinuria in OSA occurs in patients with a higher rate of sleep apneas, the lesser degree of proteinuria cannot be explained by AHI alone. Other factors that determine the severity of the disease, such as hypoxemia, merit further investigation.

Adult↗
PubMed1994

The serotonin syndrome associated with paroxetine, an over-the-counter cold remedy, and vascular disease.

There is a new, potentially fatal disorder that is infrequently reported. The apparent rareness may be because of a lack of recognition of the syndrome or its predisposing factors. Fluoxetine (Prozac, Dista Products Co, Division of Eli Lilly Co, Indianapolis, IN), sertraline (Zoloft, Roerig Division, Pfizer Inc, New York, NY), and paroxetine (Paxil, SmithKline Beecham Pharmaceuticals, Philadelphia, PA) belong to a new class of antidepressant medication: the serotonin reuptake-inhibitors (SRIs). The relative safety profile of the SRIs has led to their widespread use. However, a syndrome of excessive serotonergic activity, the "serotonin syndrome" (SS), has recently been recognized. It is characterized by changes in mental status, hypertension, restlessness, myoclonus, hyperreflexia, diaphoresis, shivering, and tremor. A high index of suspicion is required to make the diagnosis in these acutely ill patients. The most common agents implicated in SS are the monoamine oxidase inhibitors in combination with L-tryptophan or fluoxetine. A case of a patient with significant peripheral vascular disease who developed SS while taking paroxetine and an over-the-counter cold medicine is reported. There have been no prior reports of this interaction. Discontinuation of the offending agents, sedation, and supportive care are the mainstays of treatment. The interactions of serotonin with platelets and vascular endothelium are also discussed.

Acetaminophen↗
PubMed1994

Detection of yellow fever virus by polymerase chain reaction.

BACKGROUND: Yellow fever virus continues to cause major epidemics. A sensitive rapid diagnostic test is required to identify cases and contacts in order to implement emergency immunization campaigns. OBJECTIVES: To identify YFV envelope protein gene fragments, construct a polymerase chain reaction (PCR) assay and test its utility in identifying viruses isolated from laboratory and clinical specimens. STUDY DESIGN: YFV RNA was transcribed with reverse transcriptase and the cDNA amplified by PCR using primers encoding a portion of the viral envelope protein gene. The identity of the 482 bp amplified product was confirmed by restriction enzyme analysis and by dot blot hybridization with a labelled oligonucleotide probe. The assay was tested for sensitivity and specificity on isolates from South America and Africa. Detection limits were determined using different probe labels. PCR inhibitory effects were analyzed with laboratory and clinical specimens. RESULTS: The assay was specific for YFV and did not detect any of 15 other flaviviruses. The amplified region was conserved among all 32 South American and African isolates tested. Four strains from Africa did not hybridize with the probe, indicating sequence divergence in the envelope protein gene. Samples containing 30 pfu of virus were detected by visual inspection of the ethidium bromide stained 482 bp DNA amplimer and 10 pfu were detected with a digoxigenin labelled probe. Inhibitory effects of human serum on the PCR were overcome by diluting samples 4-fold in buffer. Viral neutralizing antibody in experimental samples did not affect the sensitivity of detection. Yellow fever virus in serum from experimentally infected Cynomolgus monkeys (10(3.7)-10(7.0) pfu/0.1 ml) was detected with signal intensities corresponding to the amount of virus in the sample. When YFV was added to normal human serum and held at 27 degrees C and 80% humidity, the RNA could be detected for up to 3 weeks in samples that had no infectious virus. CONCLUSIONS: A PCR assay was constructed which detected YFV RNA in isolates from patients infected in South America and Africa. This assay is specific for YFV but some African strains were not detected. More clinical samples should be tested.

Journal Article↗
PubMed1994

Medical education change: a detailed study of six medical schools.

This article reports a comparative case study of six selected USA medical schools, undertaken to identify factors that facilitate or obstruct innovation in medical education. The findings suggest that the culture of each medical school results from a combination of intra-institutional and external factors. Together these forces influence substantially the fate of educational innovations. The institutional culture influences critical elements such as educational philosophy, leadership and resources provided in support of innovation. Equally important, the culture shapes the level and type of change a school considers and implements. The findings also suggest that the availability of resources and the creative impetus present in schools giving priority to research can benefit the educational goals and facilitate educational change.

Curriculum↗
PubMed1994

Structure and regulation of the carAB operon in Pseudomonas aeruginosa and Pseudomonas stutzeri: no untranslated region exists.

The carAB operons from Pseudomonas aeruginosa PAO1 and Pseudomonas stutzeri JM300 were characterized by Southern and DNA sequence analyses. The results show that the previously reported sequence for carA (S. C. Wong and A. T. Abdelal, J. Bacteriol. 172:630-642, 1990) is derived from P. stutzeri and not P. aeruginosa, as originally reported. Therefore, the amino-terminal sequence of the purified carA product is identical to that derived from the nucleotide sequence in both organisms, P. stutzeri having four additional amino acids. The results also show that while carA and carB are contiguous in P. stutzeri, as is the case in other bacteria, they are surprisingly separated by an open reading frame (ORF) of 216 amino acids in P. aeruginosa. S1 nuclease mapping experiments with RNA extracted under a variety of growth conditions, as well as experiments using different lacZ fusions, indicate that the carA-ORF-carB operon of P. aeruginosa is transcribed from a single promoter. Moreover, these experiments demonstrate that expression of this single transcript is controlled by both arginine and pyrimidines and that variation in arginine levels specifically modulates transcriptional initiation, while pyrimidine regulation is exerted subsequent to transcriptional initiation. Modification of a rho-independent terminator-like structure, which is present upstream of carA in P. aeruginosa, removed all transcriptional sensitivity of a carA::lacZ fusion to pyrimidines. This result, when coupled with the finding that translation of an 18-amino-acid leader polypeptide (associated with this putative rho-independent terminator), is inversely proportional to pyrimidine concentration in the cell, strongly suggests that regulation of carA by pyrimidines is mediated through an attenuation-type mechanism in P. aeruginosa.

Amino Acid Sequence↗
PubMed1994

Naftidrofuryl in intermittent claudication: a retrospective analysis.

A retrospective analysis was performed on all five published clinical trials in which naftidrofuryl was given at a dosage of 600 mg daily. Two studies were undertaken in France, two in Germany, and one in Great Britain. Data for the analysis, which included the presence of risk factors, treadmill walking distances, and cardiovascular critical events that occurred during the course of the study, were generated from the patients' original study file. Included in the analysis were 888 patients, 447 receiving naftidrofuryl and 441 receiving placebo. Although there were significant differences between the studies with regard to certain variables, distribution was comparable between the treatment groups justifying an analysis on the pooled sample. An intention-to-treat analysis based on a success/failure outcome was in favor of active treatment (p = 0.003) as was an analysis of change in pain-free walking distance (PFWD) (p < 0.002). None of the risk factors had any significant influence on change in PFWD. A further analysis indicated that there were significantly fewer cardiovascular critical events in the naftidrofuryl group than in the placebo group (p = 0.029). Because the incidence of cardiovascular critical events was lower in those patients who showed the greatest improvement in PFWD, and as surgical intervention was the most frequently encountered critical event, it is possible that treatment with naftidrofuryl may lead to a reduction or postponement of surgery. Such a finding would have implications for health-care resources.

Cardiovascular Diseases↗
PubMed1993

Linkage of pyrethroid insecticide resistance to a sodium channel locus in the tobacco budworm.

Pyrethroids, with their lack of persistence and low mammalian toxicity, have been important insecticides since the early 1970s. However, heavy use has selected for resistance to pyrethroids in populations of many insects, in particular the tobacco budworm Heliothis virescens, a major cotton pest in the Americas. Several studies have identified the voltage-gated sodium channel as the principal target of pyrethroid action, and the sodium channel has been implicated in pyrethroid resistance in Musca domestica and Drosophila melanogaster. We present molecular genetic evidence that pyrethroid resistance is linked to a sodium channel locus in a strain of H. virescens. This is the first such evidence for any major agricultural pest, and is an important step towards understanding the molecular basis of resistance. This in turn will facilitate assessment, modeling, and control of resistance in pest populations, and increase our understanding of sodium channel function.

Alleles↗
PubMed1992

Neuroendocrine effects of intravenous clomipramine in depressed patients and healthy subjects.

OBJECTIVE: Neuroendocrine challenge paradigms have been used to asses serotonergic systems in depression, but limitations in the specificity of many of these tests have been noted. In this study, the neuroendocrine responses to acute intravenous administration of the serotonin (5-HT) reuptake inhibitor clomipramine were assessed in depressed patients and matched control subjects. METHODS: Thirty hospitalized patients who met DSM-III-R criteria for major depression, and 30 healthy control subjects who were matched for age, sex, and season of year for the time of study, received 12.5 mg of intravenously administered clomipramine. RESULTS: The depressed patients demonstrated significant blunting of prolactin responses to clomipramine, as well as trends toward blunted ACTH and cortisol responses. There was no difference between the patient and control groups in growth hormone responses, plasma clomipramine levels, or self-reports of side effects. CONCLUSIONS: These data support the hypothesis that depressed patients have abnormal neuroendocrine responses to the intravenous administration of the 5-HT reuptake inhibitor clomipramine. Further study is required to delineate the mechanisms responsible for the abnormal response to intravenously administered clomipramine in depression.

Adolescent↗